rs2040920

Positions:

• chr7-148093689-G-C
• chr7-148093689-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014141.6(CNTNAP2):​c.2384-24429G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,072 control chromosomes in the GnomAD database, including 12,878 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (12878 hom., cov: 32)
• Consequence: CNTNAP2 NM_014141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

CNTNAP2 (HGNC:13830): (contactin associated protein 2) This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons, and mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP2	NM_014141.6	c.2384-24429G>C		intron_variant		ENST00000361727.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP2	ENST00000361727.8	c.2384-24429G>C		intron_variant		1	NM_014141.6	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56867 AN: 151954 Hom.: 12847 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.374 AC: 56948 AN: 152072 Hom.: 12878 Cov.: 32 AF XY: 0.378 AC XY: 28078 AN XY: 74328

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.351

Alfa AF: 0.313 Hom.: 1121

Bravo AF: 0.394

Asia WGS AF: 0.517 AC: 1797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2040920; hg19: chr7-147790781;